Numerous medical therapies have attempted to treat localized disease in the body of a patient with techniques designed to direct the appropriate drug to the affected area and to avoid unacceptable or toxic side effects to healthy tissue. For example, therapies have been proposed utilizing liposomes as vehicles to carry the appropriate drugs to the diseased area.
Liposomes are microscopic particles which are made up of one or more lipid bilayers enclosing an internal compartment. They are not normally leaky but can become leaky if a hole or pore occurs in the membrane, if the membrane is dissolved or degrades, or if the membrane temperature is increased to the transition temperature, T.sub.C. The major barrier to the use of liposomes as drug carriers is making the liposome release the drugs on demand at the target sites (Science 202:1290 (1978)).
The specific use of applied heat to raise the liposome temperature to T.sub.C to make them leaky or permeable has been described (Science 204:188 (1979)). This technique has been proposed in U.S. Pat. No. 5,190,761 in which a method of activating liposomes to release their encapsulated drugs in tissue utilizing microwave radiation is described.
Additionally, it has been proposed that electroporation can be used to deliver what are normally non-permeable substances into the interior of tumor cells, thus affecting changes on an intracellular basis. Attempts to perform this delivery have only recently been successful (Ceberg et al. (1994)). One difficulty has been the confinement of the electroporation effect to the desired area. Widespread electroporation effects have been described in which not only the diseased area but also normal contralateral and normal ipsilateral brain.dagger.tissue have been affected (Salford et al. (1993)).
The currently available methods of electroporation drug delivery as described in the literature fall short of providing an effective methodology, due primarily to the inability to limit the scope of the electroporation effect to the intended target tissue. Under these circumstances, an unacceptably high level of normal tissue effect is noted and offsets the potential useful benefits of electroporation treatment.
In particular, there are a number of applications in tumor therapy, such as the treatment of glioblastoma multiforme tumors, which would benefit from a treatment methodology in which the delivery of a therapeutic agent is highly localized. At the present time, there is no cure for this uniformly fatal brain tumor which kills over 7,000 U.S. citizens each year.
Therefore, it would be desirable to have available an effective system or methodology which combines the advantage of selective drug delivery using a combination of techniques including electroporation in order to deliver drugs to selected diseased areas.